Background
Tuberculosis is a leading infectious cause of death worldwide. Novel vaccines will be required to reach global targets and reverse setbacks from the COVID-19 pandemic. We estimated the impact of novel tuberculosis vaccines in low- and middle-income countries (LMICs), under alternative delivery scenarios.
Methods
We calibrated a tuberculosis model to 105 LMICs (93% of global incidence). Vaccine scenarios were implemented as Basecase: routine vaccination of 9-year-olds and a one-time vaccination campaign for ages ≥10 with country-specific introduction between 2028[ndash]2047 and 5-year scale-up to target coverage; Accelerated Scale-up: as Basecase, but all countries introducing in 2025 with instant scale-up; and Routine Only: as Basecase, but routine vaccination only. Vaccines protected against disease for 10-years, with 50% efficacy.
Findings
The Basecase scenario reduced tuberculosis incidence (19.5% [95% uncertainty range=18.3–21.6%]) and mortality (20.6% [19.2–23.4%]) rates in 2050 and prevented 3.6 (3.3–3.9) million deaths before 2050, including 1.6 million in the WHO South-East Asian region. The Accelerated Scale-up scenario reduced tuberculosis incidence (25.2% [23.9–27.5%]), mortality (26.7% [25.2–29.9%]), and prevented 7.9 (7.3–8.5) million deaths. The Routine Only scenario reduced tuberculosis incidence (9.9% [9.0–11.6%]), mortality (9.9% [8.9–12.3%]), and prevented 1.1 (0.9–1.2) million deaths.
Interpretations
Novel tuberculosis vaccines could have substantial impact, which will vary depending on delivery strategy. Including a campaign will be crucial for rapid impact. Accelerated introduction similar to the pace of COVID-19 vaccines could approximately double the lives saved before 2050. Investment is required to support vaccine development, manufacturing, prompt introduction and scale-up.
Funding
WHO (2020/985800-0)
Background
In light of the role that airborne transmission plays in the spread of SARS-CoV-2, as well as the ongoing high global mortality from well-known airborne diseases such as tuberculosis and measles, there is an urgent need for practical ways of identifying congregate spaces where low ventilation levels contribute to high transmission risk. Poorly ventilated clinic spaces in particular may be high risk, due to the presence of both infectious and susceptible people. While relatively simple approaches to estimating ventilation rates exist, the approaches most frequently used in epidemiology cannot be used where occupancy varies, and so cannot be reliably applied in many of the types of spaces where they are most needed.
Methods
The aim of this study was to demonstrate the use of a non-steady state method to estimate the absolute ventilation rate, which can be applied in rooms where occupancy levels vary. We used data from a room in a primary healthcare clinic in a high TB and HIV prevalence setting, comprising indoor and outdoor carbon dioxide measurements and head counts (by age), taken over time. Two approaches were compared: approach 1 using a simple linear regression model and approach 2 using an ordinary differential equation model.
Results
The absolute ventilation rate, Q, using approach 1 was 2407 l/s [95% CI: 1632–3181] and Q from approach 2 was 2743 l/s [95% CI: 2139–4429].
Conclusions
We demonstrate two methods that can be used to estimate ventilation rate in busy congregate settings, such as clinic waiting rooms. Both approaches produced comparable results, however the simple linear regression method has the advantage of not requiring room volume measurements. These methods can be used to identify poorly-ventilated spaces, allowing measures to be taken to reduce the airborne transmission of pathogens such as Mycobacterium tuberculosis, measles, and SARS-CoV-2.
Background India had an estimated 2.9 million tuberculosis cases and 506 thousand deaths in 2021. Novel vaccines effective in adolescents and adults could reduce this burden. M72/AS01E and BCG-revaccination have recently completed Phase IIb trials and estimates of their population-level impact are needed. We estimated the potential health and economic impact of M72/AS01E and BCG-revaccination in India and investigated the impact of variation in vaccine characteristics and delivery strategies. Methods We developed an age-stratified compartmental tuberculosis transmission model for India calibrated to country-specific epidemiology. We projected current trends to 2050 assuming no-new-vaccine introduction, and M72/AS01E and BCG-revaccination scenarios over 2025-2050 exploring uncertainty in product characteristics and implementation. We estimated reductions in tuberculosis cases and deaths by each scenario compared to no-new-vaccine introduction, as well as costs and cost-effectiveness from health-system and societal perspectives. Results M72/AS01E scenarios were predicted to avert 40% more tuberculosis cases and deaths by 2050 compared to BCG-revaccination scenarios. Cost-effectiveness ratios for M72/AS01E vaccines were around seven times higher than BCG-revaccination, but nearly all scenarios were cost-effective. The estimated average incremental cost was US$190 million for M72/AS01E and US$23 million for BCG-revaccination per year. Sources of uncertainty included whether M72/AS01E was efficacious in uninfected individuals at vaccination, and if BCG-revaccination could prevent disease. Conclusions M72/AS01E and BCG-revaccination could be impactful and cost-effective in India. However, there is great uncertainty in impact, especially with varying vaccine characteristics. Greater investment in vaccine development and delivery is needed to raise the probability of success.
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